Up-regulation of gap junction in peripheral blood T lymphocytes contributes to the inflammatory response in essential hypertension.
Up-regulation of gap junction in peripheral blood T lymphocytes contributes to the inflammatory response in essential hypertension.
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外周血T淋巴细胞间隙连接上调有助于原发性高血压的炎症反应
DOI：
10.1371/journal.pone.0184773
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ma KT
中科院分区：
文献类型：
--
作者：
Ni X;Wang A;Zhang L;Shan LY;Zhang HC;Li L;Si JQ;Luo J;Li XZ;Ma KT
炎症在高血压发病机制中已被证明发挥着重要作用。基于连接蛋白（Cxs）的缝隙连接通道（GJCs）或半通道（HCs）参与维持免疫系统的内稳态。然而，基于Cx43的通道在T淋巴细胞中介导原发性高血压免疫反应的作用尚未完全明确。本研究旨在探究基于Cxs的通道在T淋巴细胞中对高血压介导的炎症的调节作用。通过流式细胞术检测原发性高血压患者（EHs）和血压正常的健康受试者（NTs）外周血中T淋巴细胞亚型、Cx40/Cx43以及T细胞中炎性细胞因子（IFN-γ（干扰素-γ）和TNF-α（肿瘤坏死因子-α））的表面表达，以及外周血淋巴细胞的缝隙连接通讯情况。采用蛋白质免疫印迹法分析EHs和NTs外周血淋巴细胞中Cx43蛋白的表达水平及磷酸化情况。通过CCK - 8法检测Cxs抑制剂处理后外周血单个核细胞（PBMCs）的增殖率。使用酶联免疫吸附试验（ELISA）检测炎性细胞因子水平。在CD3 + T细胞亚群中，我们发现与NTs相比，EHs外周血中CD4 + T细胞百分比、CD4 + /CD8 + 比值以及血清IFN - γ和TNF - α水平均有显著升高趋势。此外，EH患者外周血淋巴细胞表现出增强的GJCs形成、Cx43蛋白水平升高以及Ser368位点的Cx43磷酸化增加，且CD4 + 或CD8 + T淋巴细胞中Cx40/Cx43表面表达水平显著升高。模拟肽对基于Cx43的通道的抑制作用极大地减少了淋巴细胞间的染料交换、刺激后淋巴细胞的增殖以及EHs和NTs的促炎细胞因子水平。我们的数据表明，淋巴细胞中基于Cx40/Cx43的通道可能参与调节T淋巴细胞增殖和促炎细胞因子的产生，从而促进高血压炎症反应。
Inflammation has been shown to play an important role in the mechanisms involved in the pathogenesis of hypertension. Connexins (Cxs)-based gap junction channels (GJCs) or hemichannels (HCs) are involved in the maintenance of homeostasis in the immune system. However, the role of Cx43-based channels in T-lymphocytes in mediating the immune response in essential hypertension is not fully understand. The present study was designed to investigate the role of Cxs-based channels in T lymphocytes in the regulation of hypertension-mediated inflammation. The surface expressions of T lymphocyte subtypes, Cx40/Cx43, and inflammatory cytokines (IFN-γ (interferon-gamma) and TNF-ɑ (tumor necrosis factor alpha)) in T cells, as well as gap junction communication of peripheral blood lymphocytes from essential hypertensive patients (EHs) and normotensive healthy subjects (NTs) were detected by flow cytometry. Expression levels and phosphorylation of Cx43 protein in peripheral blood lymphocytes of EHs and NTs were analyzed by Western blot. The proliferation rate of peripheral blood mononuclear cells (PBMCs) after treatment with a Cxs inhibitor was examined by a CCK-8 assay. The levels of inflammatory cytokines were detected using ELISA. Within the CD3+ T cell subsets, we found a significant trend toward an increase in the percentage of CD4+ T cells and CD4+/CD8+ ratio as well as in serum levels of IFN-γ and TNF-ɑ in the peripheral blood of EHs compared with those in NTs. Moreover, the peripheral blood lymphocytes of EH patients exhibited enhanced GJCs formation, increased Cx43 protein level and Cx43 phosphorylation at Ser368, and a significant increase in Cx40/Cx43 surface expressions levels in CD4+ or CD8+ T lymphocytes. Cx43-based channel inhibition by a mimetic peptide greatly reduced the exchange of dye between lymphocytes, proliferation of stimulated lymphocytes and the pro-inflammatory cytokine levels of EHs and NTs. Our data suggest that Cx40/Cx43-based channels in lymphocytes may be involved in the regulation of T lymphocyte proliferation and the production of pro-inflammatory cytokines, which contribute to the hypertensive inflammatory response.
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影响因子：
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通讯作者：
Ezzati, Majid
影响因子：
4.8
作者：
Oviedo-Orta, E;Gasque, P;Evans, WH
通讯作者：
Evans, WH